EP0873357A2 - Agents antithrombotiques et procedes d'utilisation - Google Patents
Agents antithrombotiques et procedes d'utilisationInfo
- Publication number
- EP0873357A2 EP0873357A2 EP97903773A EP97903773A EP0873357A2 EP 0873357 A2 EP0873357 A2 EP 0873357A2 EP 97903773 A EP97903773 A EP 97903773A EP 97903773 A EP97903773 A EP 97903773A EP 0873357 A2 EP0873357 A2 EP 0873357A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- peptide
- amino acids
- amino acid
- group
- peptides
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/75—Fibrinogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/50—Cyclic peptides containing at least one abnormal peptide link
- C07K7/54—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring
- C07K7/56—Cyclic peptides containing at least one abnormal peptide link with at least one abnormal peptide link in the ring the cyclisation not occurring through 2,4-diamino-butanoic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the agents of the invention have affinity for GP-IIb/IIIa and, moreover, they have a higher apparent affinity for GP-IIb/IIIa at low calcium concentration, which is typical at the site of a clot, compared to GP-IIb/IIIa at higher, physiological calcium concentration as found elsewhere throughout the blood stream.
- GP-IIb/IIIa antagonists of the present invention are that they inhibit platelet aggregation but not significantly impair other normal platelet functions, thereby circumventing bleeding complications common to other antithrombotics.
- the one-letter and three-letter abbreviations for amino acids and derivatives thereof used herein are as follows:
- modifications to the peptide backbone and peptide bonds thereof are also encompassed within the scope of amino acid mimic or mimetic. Such modifications can be made to the amino acid, derivative thereof, non-a ino acid moiety or the peptide: either before or after the amino acid, derivative thereof or non-amino acid moiety is incorporated into the peptide. What is critical is that such modifications mimic the peptide backbone and bonds which make up the same and have substantially the same spacial arrangement and distance as is typical for traditional peptide bonds and backbones. An example of one such modification is the reduction of the carbonyl (s) of the amide peptide backbone to an amine.
- the peptides of the present invention can be synthesized by any of the suitable methods well known in the art including methods of chemical synthesis.
- the linear sequence is synthesized using commercially available automated peptide synthesizers such as those manufactured by Applied Biosystems, Inc., Foster City, CA.
- Peptides can be synthesized using amino acids or amino acid analogs, the active groups of which are protected as necessary using, for example a t- butyldicarbonate (t-Boc) group or a fluorenylmethoxy carbonyl (Fmoc) group.
- Amino acids and amino acid analogs can be purchased commercially (Sigma Chemical Co.; Advanced Chemtec) or synthesized using methods known in the art.
- Preventing platelet aggregation is essential to blocking the clotting associated with myocardial infarction, angina, stroke, angioplasty and bypass surgery.
- a particularly effective prevention of platelet aggregation is to antagonize the GP-IIb/IIIa receptor, at low calcium concentration, which is typical of wound site conditions.
- the peptides of the present invention can be used as medicaments to prevent or effectively eliminate, and thereby treat, thrombosis and thrombotic conditions by administering to a mammal exhibiting thrombosis or a thrombotic condition a therapeutically effective amount of the peptide in a suitable physiologically acceptable carrier.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Hematology (AREA)
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- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne des agents antithrombotiques qui peuvent être utilisés dans la gestion de maladies cardio-vasculaires. Les agents décrits dans cette invention consistent en de nouveaux peptides cycliques qui répondent à la formule générale (I) (N°ID. SEQ. 1) où X2 et X3 représentent indépendamment un acide aminé hydrophobe, et X4 représente un acide aminé à charge positive. Les substituants X1 et X5 représentent indépendamment zéro à cinq acides aminés, tandis que les acides aminés à terminaison amino ou carboxy d'un peptide donné peuvent être modifiés en fonction des substituants Y et Z, respectivement. Les peptides sont cyclisés avec le peptide par un pont entre les deux acides aminés, G, D et X3 étant exclus lors de la formation du pont. Les peptides correspondant à la formule susmentionnée peuvent être administrés à l'aide d'un véhicule approprié et acceptable sur le plan physiologique, ceci afin d'effectuer une thérapie dirigée contre les thromboses et les états issus du développement de thrombus.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/585,281 US5858972A (en) | 1996-01-11 | 1996-01-11 | Antithrombotic agents and methods of use |
| US585281 | 1996-01-11 | ||
| PCT/US1997/000385 WO1997025343A2 (fr) | 1996-01-11 | 1997-01-10 | Agents antithrombotiques et procedes d'utilisation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0873357A2 true EP0873357A2 (fr) | 1998-10-28 |
Family
ID=24340782
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP97903773A Withdrawn EP0873357A2 (fr) | 1996-01-11 | 1997-01-10 | Agents antithrombotiques et procedes d'utilisation |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US5858972A (fr) |
| EP (1) | EP0873357A2 (fr) |
| JP (1) | JP2000503649A (fr) |
| AU (1) | AU1825697A (fr) |
| CA (1) | CA2242385A1 (fr) |
| WO (1) | WO1997025343A2 (fr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19728524A1 (de) * | 1997-07-04 | 1999-01-07 | Merck Patent Gmbh | Cyclische Azapeptide |
| MXPA03001721A (es) | 2000-08-30 | 2003-05-27 | Hoffmann La Roche | Peptidos ciclicos selectivos. |
| CA2475761C (fr) * | 2002-02-11 | 2011-07-12 | Gold-T Tech, Inc. | Dispositif implantable produisant des ultrasons a haute frequence dans le but de favoriser l'ecoulement sanguin et de prevenir la formation d'un caillot |
| DK1480998T3 (da) * | 2002-02-27 | 2007-03-26 | Ferring Bv | Mellemprodukter og fremgangsmåder til fremstilling af heptapeptidoxytocinanaloger |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ235564A (en) * | 1989-10-13 | 1993-10-26 | Merck & Co Inc | Fibrinogen receptor antagonist and pharmaceutical compositions |
| JPH05509294A (ja) * | 1990-04-06 | 1993-12-22 | ラ ホヤ キャンサー リサーチ ファウンデーション | 血栓症治療のための方法および組成物 |
| ATE466869T1 (de) * | 1993-03-05 | 2010-05-15 | Epimmune Inc | Verfahren zur herstellung von immunogenen hla- a2.1-bindenden peptiden |
| WO1994025071A1 (fr) * | 1993-05-05 | 1994-11-10 | Keith Rose | Composes de polyoximes et leur preparation |
| DE69425745T2 (de) * | 1993-06-18 | 2001-04-19 | La Jolla Cancer Research Foundation, La Jolla | Verfahren und zusammensetzungen zur behandlung der thrombose |
| US5770565A (en) * | 1994-04-13 | 1998-06-23 | La Jolla Cancer Research Center | Peptides for reducing or inhibiting bone resorption |
-
1996
- 1996-01-11 US US08/585,281 patent/US5858972A/en not_active Expired - Lifetime
-
1997
- 1997-01-10 CA CA002242385A patent/CA2242385A1/fr not_active Abandoned
- 1997-01-10 WO PCT/US1997/000385 patent/WO1997025343A2/fr not_active Application Discontinuation
- 1997-01-10 EP EP97903773A patent/EP0873357A2/fr not_active Withdrawn
- 1997-01-10 JP JP9525416A patent/JP2000503649A/ja active Pending
- 1997-01-10 AU AU18256/97A patent/AU1825697A/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO9725343A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US5858972A (en) | 1999-01-12 |
| WO1997025343A3 (fr) | 1997-09-18 |
| JP2000503649A (ja) | 2000-03-28 |
| WO1997025343A2 (fr) | 1997-07-17 |
| CA2242385A1 (fr) | 1997-07-17 |
| AU1825697A (en) | 1997-08-01 |
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